Effects of phenytoin on cell-mediated immunity

Phenytoin is a highly effective anticonvulsant agent that is widely administrated to prevent some kinds of patients with brain tumor. But it has been said that phenytoin may have some immunosuppresive potential for hosts. In this study, we evaluated the effects of phenytoin upon cellular immunity such as NK, CTL and LAK activity in murine models. Fresh splenocytes were taken out from mice (CBA/J, C 3 H/HeN, C 57 BL/6) into which phenytoin had been injected intraperitoneally at a daily dose of 1,000 micrograms for 28 days. The serum concentration of phenytoin in the experimental models was 10-20 micrograms/ml. The cytotoxic activities were estimated by a 4-hr 51Cr release assay. The mitogen-stimulated lymphocyte function was evaluated by 3H-thymidine incorporation into DNA. The NK activity was estimated by cytotoxicity of splenocytes of CBA/J mice against NK-sensitive YAC-1 cells. The cytotoxic T-lymphocyte (CTL) activity was estimated by cytotoxicity of splenocytes of C 57 BL/6 mice which were stimulated in vitro for 5 days by splenocytes of C 3H/HeN treated with mitomycin C, against RSV-M glioma cells. Lymphokine-activated killer (LAK) activity was estimated by cytotoxicity of LAK cells, which were induced from splenocytes of C 3 H/HeN mice by human recombinant interleukin-2 (rIL-2), against syngeneic RSV glioma and allogeneic 203 glioma cells. 3H-thymidine incorporation of splenocytes of C 57 BL/6 mice was reduced significantly (p less than 0.01) in phenytoin-treated mice. The cytotoxicity of splenocytes of non-treated CBA/J mice against YAC-1 cells was 75%, but that of phenytoin-treated CBL/J mice was a few %.(ABSTRACT TRUNCATED AT 250 WORDS)